7366-56-5Relevant articles and documents
5,8-DISUBSTITUTED-[1,2,4]TRIAZOLO[1,5-A]PYRIDINYL AND 5,8-DISUBSTITUTED-IMIDAZO[1,2-A]PYRIDINE DERIVATIVES USEFUL AS INHIBITORS OF ENTEROPEPTIDASE
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Page/Page column 141, (2021/01/29)
The present invention is directed to 5,8-disubstituted-[1,2,4]triazolo[1,5- a]pyridinyl and 5,8-disubstituted-imidazo[1,2-a]pyridine derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the enteropeptidase enzyme.
2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 1. Identification of an Allosteric Binding Site
Bestgen, Beno?t,Krimm, Isabelle,Kufareva, Irina,Kamal, Ahmed Ashraf Moustafa,Seetoh, Wei-Guang,Abell, Chris,Hartmann, Rolf W.,Abagyan, Ruben,Cochet, Claude,Le Borgne, Marc,Engel, Matthias,Lomberget, Thierry
, p. 1803 - 1816 (2019/03/07)
CK2 is a ubiquitous Ser/Thr protein kinase involved in the control of various signaling pathways and is known to be constitutively active. In the present study, we identified aryl 2-aminothiazoles as a novel class of CK2 inhibitors, which displayed a non-ATP-competitive mode of action and stabilized an inactive conformation of CK2 in solution. Enzyme kinetics studies, STD NMR, circular dichroism spectroscopy, and native mass spectrometry experiments demonstrated that the compounds bind in an allosteric pocket outside the ATP-binding site. Our data, combined with molecular docking studies, strongly suggested that this new binding site was located at the interface between the αC helix and the flexible glycine-rich loop. A first hit optimization led to compound 7, exhibiting an IC50 of 3.4 μM against purified CK2α in combination with a favorable selectivity profile. Thus, we identified a novel class of CK2 inhibitors targeting an allosteric pocket, offering great potential for further optimization into anticancer drugs.
Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D polymerase against foot-and-mouth disease (FMD)
Jeong, Kwi-Wan,Lee, Jung-Hun,Park, Sun-Mi,Choi, Joo-Hyung,Jeong, Dae-Youn,Choi, Dong-Hwa,Nam, Yeonju,Park, Jong-Hyeon,Lee, Kwang-Nyeong,Kim, Su-Mi,Ku, Jin-Mo
, p. 387 - 397 (2015/09/01)
Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of livestock caused by a highly variable RNA virus, foot-and-mouth disease virus (FMDV). One of the targets to suppress expansion of and to control FMD is 3D polymerase (FMDV 3Dpol). In this study, 2-amino-4-arylthiazole derivatives were synthesized and evaluated for their inhibitory activity against FMDV 3Dpol. Among them, compound 20i exhibited the most potent functional inhibition (IC50 = 0.39μM) of FMDV 3D polymerase and compound 24a (EC50=13.09 μM) showed more potent antiviral activity than ribavirin (EC50=1367 μM) and T1105 (EC50=347 μM) with IBRS-2 cells infected by the FMDV O/SKR/2010 strain.